ArticleThe Journal of biological chemistry2012
BMP2 protein regulates osteocalcin expression via Runx2-mediated Atf6 gene transcription.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 108 papers.
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Who cites it
108 citing papers in PubMed, 203 citations in OpenAlex.
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- Visible-light-triggered BMP-2 release from enzymatically crosslinked marine collagen-alginate hydrogel blends enhances osteogenesis in dental pulp stem cells.Frontiers in physiology · 2026Article
- Understanding the molecular basis of mesenchymal stem cell stemness: implications for clinical applications.Cell death & disease · 2025Review
- Autophagy, ER-phagy and ER Dynamics During Cell Differentiation.Journal of molecular biology · 2025Review
- Elevation of master autophagy regulator Tfeb in osteoblast lineage cells increases bone mass and strength.JCI insight · 2025Article
- The role of the unfolded protein response pathway in bone homeostasis and potential therapeutic target in cancer-associated bone disease.Bone research · 2025Review
- Molecular mechanisms underlying the effects of statins on bone metabolism: an evolving paradigm of statins delivery modalities for bone regeneration.Pharmacological reports : PR · 2025Review
- SEC24D depletion induces osteogenic differentiation deficiency by inactivating the ATF6/TGF-β/Runx2 regulatory loop.Communications biology · 2025Article
- Optimization and Implication of Adipose-Derived Stem Cells in Craniofacial Bone Regeneration and Repair.Bioengineering (Basel, Switzerland) · 2024Review
- Placental Tissue Calcification and Its Molecular Pathways in Female Patients with Late-Onset Preeclampsia.Biomolecules · 2024Article
- Stimuli-responsive microcarriers and their application in tissue repair: A review of magnetic and electroactive microcarrier.Bioactive materials · 2024Review
- Enhancing bone regeneration: Unleashing the potential of magnetic nanoparticles in a microtissue model.Journal of cellular and molecular medicine · 2024Article
- Expression profile of viability and stress response genes as a result of resveratrol supplementation in vitrified and in vitro produced cattle embryos.Molecular biology reports · 2024Article
- Intersections of Fibrodysplasia Ossificans Progressiva and Traumatic Heterotopic Ossification.Biomolecules · 2024Review
- Article
- Design, synthesis and biological evaluation of novel pyrimidine derivatives as bone anabolic agents promoting osteogenesisRSC medicinal chemistry · 2024Article
- Exploring the Osteogenic Potential of Zinc-Doped Magnesium Phosphate Cement (ZMPC): A Novel Material for Orthopedic Bone Defect Repair.Biomedicines · 2024Article
- Comparison of the differentiation of ovine fetal bone-marrow mesenchymal stem cells towards osteocytes on chitosan/alginate/CuO-NPs and chitosan/alginate/FeO-NPs scaffolds.Scientific reports · 2024Article
48 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Bone morphogenetic protein 2 (BMP2) activates unfolded protein response (UPR) transducers, such as PERK and OASIS, in osteoblast cells. ATF6, a bZIP transcription factor, is also a UPR transducer. However, the involvement of ATF6 in BMP2-induced osteoblast differentiation has not yet been elucidated. In the present study, BMP2 treatment was shown to markedly induce the expression and activation of ATF6 with an increase in alkaline phosphatase (ALP) and OC expression in MC3T3E1 cells. In contrast, ATF6 activation by BMP2 was not observed in the Runx2(-/-) primary calvarial osteoblasts, and Runx2 overexpression recovered BMP2 action. BMP2 stimulated ATF6 transcription by enhancing the direct binding of Runx2 to the osteoblast-specific cis-acting element 2 (OSE2, ACCACA, -205 to -200 bp) motif of the Atf6 promoter region. In addition, the overexpression of ATF6 increased the Oc promoter activity by enhancing the direct binding to a putative ATF6 binding motif (TGACGT, -1126 to -1121 bp). The inhibition of ATF6 function with the dominant negative form of ATF6 (DN-ATF6) blocked BMP2- or Runx2-induced OC expression. Interestingly, OASIS, which is structurally similar to ATF6, did not induce Oc expression. ALP and Alizarin red staining results confirmed that BMP2-induced matrix mineralization was also dependent on ATF6 in vitro. Overall, these results suggest that BMP2 induces osteoblast differentiation through Runx2-dependent ATF6 expression, which directly regulates Oc transcription.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.